plasminogen-activator-inhibitor-2 and Disease-Models--Animal

A Pseudomonas aeruginosa quorum-sensing system, which produces N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C

Topics: 4-Butyrolactone; Acute Disease; Analysis of Variance; Animals; Biopsy, Needle; Disease Models, Animal; Female; Homoserine; Immunohistochemistry; Neutrophils; Pseudomonas aeruginosa; Random Allocation; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Wound Healing; Wounds and Injuries

Dimethyl sulfoxide (DMSO) is commonly used as a solvent to dissolve water-insoluble drugs or other test samples in both in vivo and in vitro experiments. It was observed during our experiment that DMSO at noninhibitory concentrations could significantly inhibit pyocyanin production in the human pathogen Pseudomonas aeruginosa Pyocyanin is an important pathogenic factor whose production is controlled by a cell density-dependent quorum-sensing (QS) system. Investigation of the effect of DMSO on QS showed that DMSO has significant QS antagonistic activities and concentrations of DMSO in the micromolar range attenuated a battery of QS-controlled virulence factors, including rhamnolipid, elastase, and LasA protease production and biofilm formation. Further study indicated that DMSO inhibition of biofilm formation and pyocyanin production was attained by reducing the level of production of an autoinducer molecule of the rhl QS system, N-butanoyl-l-homoserine lactone (C

Topics: 4-Butyrolactone; Animals; Anti-Bacterial Agents; Biofilms; Dimethyl Sulfoxide; Disease Models, Animal; Female; Gene Expression Regulation, Bacterial; Glycolipids; Metalloproteases; Mice, Inbred C57BL; Pseudomonas aeruginosa; Pseudomonas Infections; Pyocyanine; Virulence Factors; Wound Infection

Cis-2-dodecenoic acid (BDSF) is well known for its important functions in intraspecies signaling in Burkholderia cenocepacia. Previous work has also established an important role of BDSF in interspecies and inter-kingdom communications. It was identified that BDSF modulates virulence of Pseudomonas aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still not clear.. We report here that BDSF mediates the cross-talk between B. cenocepacia and P. aeruginosa through interference with quorum sensing (QS) systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results revealed that exogenous addition of BDSF not only reduced the transcriptional expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and rhlR, but also simultaneously decreased the production of QS signals including 3-oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently resulting in the down-regulation of biofilm formation and virulence factor production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.. These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.

Topics: 4-Butyrolactone; Animals; Antibiosis; Bacterial Secretion Systems; Biofilms; Burkholderia cenocepacia; Disease Models, Animal; Epithelial Cells; Fatty Acids, Monounsaturated; Gene Expression Profiling; HeLa Cells; Homoserine; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolones; Quorum Sensing; Signal Transduction; Virulence; Virulence Factors; Zebrafish